UTAA06

Purpose: To evaluate the safety, pharmacokinetics, and preliminary clinical activity of UTAA06, an "off-the-shelf" allogeneic B7-H3-targeted chimeric antigen receptor (CAR)-Vδ1T cell therapy, in patients with pretreated, advanced B7-H3-positive solid tumors. Patients and Methods: In this first-in-human, phase I, dose-escalation study (NCT06372236), ten patients with advanced solid tumors (including gastric, colorectal, hepatocellular, ovarian, and neuroendocrine cancers) were enrolled. Following lymphodepletion chemotherapy (cyclophosphamide and fludarabine), patients received UTAA06 infusion across three dose levels (5×10⁸, 8×10⁸, or 1×10⁹ cells). The primary endpoint was safety. Secondary endpoints included pharmacokinetics and anti-tumor efficacy. Results: UTAA06 demonstrated a manageable safety profile; no graft-versus-host disease (GvHD) was observed, and cytokine release syndrome (CRS) was limited to two transient Grade 1 events. A single dose-limiting toxicity (Grade 3 pneumonitis) was reported in one patient at the 5×10⁸ cells dose level. While UTAA06 demonstrated signals of biological activity, including transient reductions in serum tumor markers in 50% of patients, no objective response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria was observed. Further analysis identified that the limited CAR-T cell persistence was likely driven by subclinical host-versus-graft rejection (HvGR). Conclusions: This study provides clinical proof-of-concept for allogeneic B7-H3-targeted CAR-Vδ1T cells as a safe platform with low risk of GvHD and demonstrable biological activity in solid tumors. However, clinical efficacy was constrained by limited cellular persistence caused by host immune rejection. Future strategies are required to enhance the durability and therapeutic potential of this allogeneic approach.